Nimbolide Induces ROS-Regulated Apoptosis and Inhibits Cell Migration in Osteosarcoma

International Journal of Molecular Sciences

Ju-Fang Liu²  Chun-Han Hou⁴  Feng-Ling Lin³  Ya-Ting Tsao⁴  Sheng-Mou Hou¹ 

[1] Department of Orthopedic Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, No. 95, Wenchang Road, Shilin District, Taipei 11101, Taiwan;Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan; E-Mail:;Department of Dermatology, Sijhih Cathay General Hospital, Taipei 22174, Taiwan; E-Mail:;Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei 10617, Taiwan; E-Mails:

关键词: osteosarcoma;    apoptosis;    endoplasmic reticulum stress;    reactive oxygen species;    migration;   

DOI  :  10.3390/ijms161023405

来源: mdpi

【 摘 要 】

Osteosarcoma (OS) is a primary malignant tumor of bone and is most prevalent in children and adolescents. OS is frequently associated with pulmonary metastasis, which is the main cause of OS-related mortality. OS has a poor prognosis and is often unresponsive to conventional chemotherapy. In this study, we determined that Nimbolide, a novel anti-cancer therapy, acts by modulating multiple mechanisms in osteosarcoma cells. Nimbolide induces apoptosis by increasing endoplasmic reticulum (ER) stress, mitochondrial dysfunction, accumulation of reactive oxygen species (ROS), and finally, caspase activation. We also determined that Nimbolide inhibits cell migration, which is crucial for metastasis, by reducing the expression of integrin αvβ5. In addition, our results demonstrate that integrin αvβ5 expression is modulated by the PI3K/Akt and NF-κB signaling cascade. Nimbolide has potential as an anti-tumor drug given its multifunctional effects in OS. Collectively, these results help us to understand the mechanisms of action of Nimbolide and will aid in the development of effective therapies for OS.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.